Diminished glucose tolerance is a characteristic of the elderly individual. However, its metabolic basis and health significance remains unclear. In these sudies we are exploring quantitative aspects of whole body glucose metabolism with the aid of stable isotopes (13C, 2H). These techniques allow similar studies to be conducted in young adults and thus provides an opportunity to examine, in detail, responses of glucose metabolism (endogenous production, oxidation, recylcing, disappearance) to various stimuli (diet, glucose infusion) in subjects of increasing adult age. Studies on the effects of variable levels of glucose infusion in young adults and in healthy elderly subjects (70-80 yr.) have been undertaken. These studies indicate that the responses and regulation of hepatic glucose production to intravenous glucose infusion are similar in young adults and elderly subjects. Thus, the deterioration in glucose tolerance is due to alterations in peripheral tissues, possibly related to reduced sensitivity to insulin. Studies are underway to exlore the impact of altered glucose metabolism on the metabolism of amino acids, as a further basis for evaluating the metabolic consequences of the changes in glucose metabolism with aging.